Synthesis of Chlorophyll A

Structure of Chlorophyll A

C55H72MgN4O5

Principal investigatorRobert B. Woodward
Publication year1960
Synthesis typeFormal
Number of steps 49 (7 parts)
References
Part 1 of 7
intermediate structure
  1. NaNO2
  2. Zn
AcOH, H2O
4 to 100 °C, 5.5 h, 57-61%
intermediate structure
Part 2 of 7
intermediate structure
H2SO4
40 °C, 20 min, 90%
intermediate structure
HO(CH2)2NH2
170 °C, 60 min, 84-87%
intermediate structure
POCl3
DMF
0 to 95 °C, 2.5 h, 90-96%
intermediate structure
H2C(CN)2, Et2NH
EtOH
50 to 100 °C, 10 min, 95-98%
intermediate structure
Br2
MeOH, H2O
Reflux, 4 min, 68-70%
intermediate structure
NaOH
H2O
100 °C, 3.5 h, 83%
intermediate structure
MeNO2, Et2NH
EtOH
Reflux, 2.5 h, 68%
See the Henry Reaction
intermediate structure
NaBH4, NaHCO3
H2O
RT, 40 min, 87%
intermediate structure
NaOAc.3H2O, KOAc
100-135 °C, 25 min, 50-58%
intermediate structure
H2, PtO2
MeOH
RT, 3 h, 85-93%
intermediate structure
Part 3 of 7
intermediate structure
AcCl, AlCl3
CH2Cl2
Reflux, 2 h, 86%
"The starting material is an intermediate of the second part of this synthesis."
intermediate structure
NH2NH2.H2O, NaOH
Triethylene glycol
Reflux, 2 h, 63-83 &
intermediate structure
POCl3
DMF
-30 °C, 20 min, 89%
intermediate structure
H2C(CN)2, Et2NH
EtOH
100 °C, 60 min, 97%
intermediate structure
SO2Cl2
AcOH
55 °C, 90 min, 84%
intermediate structure
Part 4 of 7
intermediate structure
  1. Br2
  2. SO2Cl2
  3. H2O
AcOH
0 to 60 °C, 6.5 h, 70-75%
intermediate structure
Cu-Bronze
230-240 °C, 60 min, 72%
intermediate structure
KOH
EtOH, H2O
Reflux, 2.5 h, 90%
intermediate structure
Cu-Bronze
220-240 °C, 60 min, 80%
intermediate structure
Part 5 of 7
intermediate structure
Malonic Acid, PhNH2
EtOH
Reflux, 8 h, 70-75%
"The starting material is an intermediate of the second part of this synthesis."
intermediate structure
H2, Ni (Raney), NaOH
H2O
RT, 12 h, 90-92%
intermediate structure
  1. SO2Cl2
  2. H2O
Et2O
-15 °C to RT, ON, 85-90%
intermediate structure
NaOH
H2O
180 °C, 90 min
intermediate structure
CH2N2
MeOH, Et2O
RT, , 75-80% (2 steps)
intermediate structure
POCl3, DMF
DCE
-10 °C to RT, 40 min, 71%
intermediate structure
Part 6 of 7
intermediate structure + intermediate structure
HCl
EtOH, H2O
Reflux, 60 min, 55%
intermediate structure + intermediate structure
ZnCl2
CH2Cl2
Reflux, 2 h, 79%
intermediate structure
NaOH
H2O
95 °C, 15 min
intermediate structure
CH2N2
MeOH, H2O
RT, 90 min, 84% (2 steps)
intermediate structure
EtNH2, HBr
AcOH, H2O
0 °C, 45 min, 94%
intermediate structure
H2S, NaOMe
PhH, MeOH
RT, 5 min, 86%
intermediate structure
Part 7 of 7
intermediate structure + intermediate structure
HBr
MeOH, Et2O, H2O
-25 to 0 °C, , 56%
intermediate structure
NaBH4
H2O
RT
intermediate structure + intermediate structure
  1. HCl
  2. I2
CH2Cl2, PhH, MeOH
RT, 60 min
intermediate structure
Ac2O
Pyr
50-55 °C, 60 min, 48% (3 steps)
intermediate structure
O2
AcOH
95 °C, 60 min, 91%
intermediate structure
AcOH
Reflux, 31.5 h, 59%
intermediate structure
HCl
MeOH, H2O
Reflux, 18 h, 75%
intermediate structure
Me2SO4, NaOH
H2O
Reflux, 2.5 h, 84%
intermediate structure
O2
CH2Cl2
0 °C, 35 min, 59%
intermediate structure
KOH
MeOH, CH2Cl2
RT, 60 min, 22%
intermediate structure
NaOH
Dioxane , H2O
RT, 12 h
"The enantiomers were resolved with (-)-Quinine (4 % yield)."
intermediate structure
CH2N2
MeOH, Et2O
RT, 20 min, 60% (2 steps)
"Relay point."
intermediate structure
HCN, Et3N
CH2Cl2
0 °C to RT, 5 min, 78%
intermediate structure
Zn
AcOH, CH2Cl2
RT, 1 min
intermediate structure
CH2N2
MeOH, Et2O
RT, 10 min, 9% (2 steps)
intermediate structure
HCl
MeOH
0 °C to RT, 16 h, 36%
intermediate structure
Remaining...
23% (4 steps)
"See: Fortschr. Chem. Forsch. 1952, 2, 538 and Tetrahedron 1981, 37, 399."
intermediate structure